Affective disorders depression and bipolar disease

Major depression (see 6.03 Affective Disorders: Depression and Bipolar Disorders) is a chronic disorder that affects 10-25% of females and 5-12% of males. Suicide in 15% of chronic depressives makes it the ninth leading cause of death in the USA. Presenting complaints for depression include: depressed or irritable mood, diminished interest or pleasure in daily activities, weight loss, insomnia or hypersomnia, fatigue, diminished concentration, and recurrent thoughts of death. The World Health Organization (WHO) has estimated that approximately 121 million individuals worldwide suffer from depression and that depression will become the primary disease burden worldwide by 2020. In the majority of individuals episodes of depression are acute and self-limiting. The genetics of major depression are not well understood and have focused on functional polymorphisms related to monoaminergic neurotransmission as the majority of effective antidepressants act by facilitating monoamine availability. Positive associations have been reported between the polymorphism in the serotonin transporter promoter region (5HT TLPR)10 and bipolar disorder, suicidal behavior, and depression-related personality traits but not to major depression. There is preliminary data on the association of polymorphisms in brain-derived neurotrophic factor (BDNF) and depression. However, these are controversial.22

Other mood disorders include bipolar affective disorder (BPAD) and dysthymia. BPAD is diagnosed by discrete periods of abnormal mood and activity that define depressive and manic or hypomanic episodes and occurs in 10% of individuals with major depression. BPAD occurs as two types, I and II, the latter having a familial association and a higher incidence of hypomania. Dysthymia is a chronically depressed mood, usually present for 2 years or more, that does not warrant a diagnosis as major depression.

Depression has traditionally been treated by drugs and electroconvulsive therapy (ECT). The initial drugs to treat depression, the monoamine oxidase inhibitors (MAOIs), e.g., isoniazide, were found by serendipity,11 and from these second-generation MAOIs, e.g., phenelzine, tranylcypromine, and the tricyclic antidepressants (TCAs) were developed and include impramine, desipramine, amitriptyline, etc. The latter are monoamine uptake inhibitors and while highly efficacious, have limiting side effects. Current treatment modalities for depression include more selective monoamine uptake blockers, and include: the SSRIs (selective 5HTuptake blockers), fluoxetine, sertraline, citalopram, paroxetine, etc., the SNRIs (serotonin norepinephrine reuptake inhibitors) that include venlfaxine, nefazodone, and mitrazepine. BPAD is typically treated with mood stabilizers including lithium and valproate, the mechanisms of action of which are currently becoming clearer.

The prognosis for patients diagnosed with major depressive disorders is relatively good with 70-80% of patients exhibiting significant favorable response to treatment. By comparison, the prognosis for bipolar disorder patients is poor. Only 50-60% of BPAD patients gain control of their symptoms with currently available therapies, and a mere 7% become symptom free.

Bipolar Disorder Uncovered

Bipolar Disorder Uncovered

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